The present invention relates to a method for comminuting concretions located within a living body using time-synchronized, multi-pulsed acoustic shock waves, to suppress cavitation bubble expansion for the reduction of vascular injury produced by lithotripter shock waves.
Extracorporeally generated shock waves are presently used clinically for the fragmentation and comminution of kidney and ureteral stones, a process called shock wave lithotripsy (SWL). Despite its widespread success, SWL as it is currently carried out can also cause renal injury, such as hematuria, kidney enlargement, and renal and perirenal hemorrhage and hematomas. Furthermore, the long-term clinical consequence of SWL on renal function is still under investigation. Renal injury in SWL is primarily vascular lesions, characterized by extensive damage of the endothelial cells and the rupture of blood vessels, with capillary and small blood vessels much more susceptible to SWL injury than large vessels. While most patients with normal renal function recover well following lithotripsy, there are subgroups of patients who are at much higher risk for chronic SWL injury. These include patients with solitary kidneys, pre-existing hypertension, and, in particular, pediatric and elderly patients.
In the past two decades, shock wave lithotripsy (SWL) has been used routinely as a treatment modality for the majority of stone patients. Clinical and animal studies, however, have also demonstrated that SWL is accompanied by some forms of renal injury, such as hematuria, formation of diffuse hemorrhage and multiple hematomas within the renal parenchyma, perirenal fat, and subcapsular connective tissue, as well as kidney edema. The injury is primarily vascular lesions, with extensive damage to the endothelial cells and rupture of capillaries and small blood vessels. In young adult patients, the vascular injury associated with SWL only affects about 2.0% of their functional renal mass. Therefore, most of these patients recover following the treatment without significant clinical consequences. There are, however, subgroups of patients who are at much higher risk for chronic injury following SWL. Therefore, there is clearly a clinical need to improve the safety of SWL treatment.
One primary mechanism that leads to vascular injury in SWL is the mechanical dilation of the capillaries and small blood vessels by the large, rapid intraluminal expansion of cavitation bubbles. It is now known that if such a large intraluminal bubble expansion is suppressed and, for example by the inversion of the lithotripter shock waveform, vascular injury will be minimized. Normal lithotripter shock waves consist of a leading compressive wave followed by a tensile wave. In an inverted lithotripter shock wave, the tensile wave precedes the compressive wave. Unfortunately, inverted lithotripter shock waves do not break up kidney stones; and therefore cannot be successfully used for SWL. Clearly, there is a need for SWL that can significantly suppress cavitation bubble expansion while maintaining effective stone comminution efficiency.
Zhong et al. in U.S. Pat. No. 5,582,578 disclose a method for the comminution of concretions in vivo by controlling and concentrating cavitation energy, utilizing two shock wave pulses. In the method disclosed by Zhong et al. the second pulse forces the complete collapse of cavitation bubble cluster produced by the first pulse in such a way that the cavitation collapse energy is directed towards the target concretion and thereby reducing tissue injury caused by random collapse of cavitation bubbles. However, in the method disclosed by Zhong et al., the second shock wave pulse is produced after a delay of more than 50 xcexcs delay from the time of the first shock wave arrives at the focus of a lithotripter and therefore causes complete bubble collapse because at this point in time cavitation bubbles are at or near to their maximum expansion. However, Zhong et al. do not disclose or discuss the beneficial effect of an interpulse delay that is shorter than 50 xcexcs that has now been unexpectedly and surprisingly discovered to restrain the further expansion of cavitation bubbles.
The present invention provides a method for generating time-synchronized, multi-pulsed shock waves, which are controlled in their respective pressure amplitudes and which have a specified extremely short interpulse time delay (0.5 to 21 microseconds) and specified pressure relationships between the compressive and tensile components of the individual pulses to provide a means of inducing an inertial cavitation bubble cluster while suppressing the growth, but not the collapse, of cavitation bubbles in tissue surrounding the target concretion in vivo to achieve stone comminution with reduced tissue injury.
It is therefore an object of the present invention to control precisely the profile and sequence of the acoustic shock wave pulses produced by a lithotripter to achieve effective stone comminution in SWL while at the same time drastically reducing tissue injury.
Some of the objects of the invention having been stated hereinabove, and which are addressed in whole or in part by the present invention, other objects will become evident as the description proceeds when taken in connection with the accompanying drawings as best described hereinbelow.